Dextromethorphan is a pharmaceutical used, for example, as an over the counter cough suppressant. It provides a bitter off-note/aftertaste, which makes patient compliance problematic. Therefore, methods that are able to identify compounds or ingredients that are able to modulate, and in particular to inhibit or mask, this bitter aftertaste are of interest.
Bitter taste is perceived via taste receptors, and a family of 25 functional bitter taste receptors (TAS2R or T2R) is known. The receptors are broadly tuned to detect thousands of structurally diverse bitter substances, and no obvious shared chemical features can be recognized for the agonists even of single receptors. For example, TAS2R46 is known to respond to certain sesquiterpene lactones, certain clerodane and labdane diterpenoids, strychnine and denatonium.
None of these bitter taste receptors had previously been shown to be activated by dextromethorphan.
Applicant found that one of these receptors is activated by dextromethorphan.
In particular, applicant identified dextromethorphan as a specific agonist of taste receptor type 2 member 46 (TAS2R46).
This finding allows to provide methods that employ TAS2R46 and its agonist dextromethorphan to identify ingredients that modulate the response of TAS2R46 to dextromethorphan, for example, antagonists (blockers, inhibitors or masking agents) of the dextromethorphan-dependent TAS2R46 activation. The methods therefore allow to identify modulators including agents that reduce, block or mask the bitter taste of dextromethorphan. Identified agents can be confirmed in human sensory evaluations and will allow to reduce the bitter aftertaste of dextromethorphan.